Determination of four antiepileptic drugs with solvent assisted dispersive solid phase microextraction – Gas chromatography–mass spectrometry in human urine samples

Abstract

In this paper solvent assisted dispersive solid-phase microextraction (SA-DSPME) as a rapid and comprehensive sample preparation method was developed to extract and cleanup four antiepileptic drugs (AEDs); valproic acid, phenobarbital, levetiracetam, and pregabalin from human urine samples. In the procedure, the dispersion of the sorbent was attained by rapid injection of a mixture of the adsorbent and disperser solvent into the aqueous sample to increase the contact surface and reduce the extraction time and amount of sorbent consumption. Several sorbents such as magnetic Fe3O4, Fe3O4@graphene, Fe3O4@graphene oxide, Fe3O4@MWCNTs, Fe3O4@SiO2, Fe3O4@SiO2@TiO2, Fe3O4@Chitosan, and NiO NPs were tested to extract the target drugs and the results compared. Among them, Fe3O4@SiO2 was chosen as the best sorbent, and its structure characterized using FESEM, FTIR, and EDX. Besides, effective factors in the SA-DSPME, including the type of disperser solvent and desorption solvent, extraction time, desorption time, pH, and disperser solvent and desorption solvent volume, were optimized using one factor at a time and design experiment strategy. Under the optimum conditions, the calibration curves were linear in the range of 0.2–100 ng mL−1 for valproic acid and phenobarbital, and 0.4–120 ng mL−1 for levetiracetam and pregabalin. Limit of detections and limit of quantifications were lower than 0.11 and 0.4 ng mL−1 for the analytes. Besides, the procedure showed suitable relative standard deviations (≤3.8%) and preconcentration factors (≥133.9) for the determination of the antiepilepsy drugs. Analysis of human urine samples confirmed that the SA-DSPME-GC procedure is an appropriate method for measuring the target drugs in biological samples with recoveries between 92.9 and 103.2 % and RSD less than 4.7%.